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Obesity is a major public health issue that is associated with metabolic diseases including diabetes mellitus type 2 and metabolic syndrome. This pathology leads to detrimental cardiovascular health and secondary effects, such as lipotoxicity, inflammation, and oxidative stress. Recently, extracellular vesicles (EVs) have been highlighted as novel players participating in human physiology and pathophysiology. In obesity, adipose tissue is related to the active shedding of adipocyte-derived extracellular vesicles (AdEVs). The current review explores and highlights the role of AdEVs and their cargo in obesity and metabolic syndrome. AdEVs are proposed to play an important role in obesity and its comorbidities. AdEVs are biological nanoparticles mainly shed by visceral and subcutaneous adipose tissue, acting in physiological and pathophysiological conditions, and also carrying different cargo biomolecules, such as RNA, microRNA (miRNA), proteins, and lipids, among others. RNA and miRNA have local and systemic effects affecting gene expression in target cell types via paracrine and endocrine actions. State of the art analyses identified some miRNAs, such as miR-222, miR-23b, miR-4429, miR-148b, and miR-4269, that could potentially affect cell pathways involved in obesity-related comorbidities, such as chronic inflammation and fibrosis. Similarly, AdEVs-proteins (RBP4, perilipin-A, FABP, mimecan, TGFBI) and AdEVs-lipids (sphingolipids) have been linked to the obesity pathophysiology. The current knowledge about AdEVs along with further research would support and reveal novel pathways, potential biomarkers, and therapeutic options in obesity.

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A large proportion of patients with low-renin hypertension (LRH) correspond to primary aldosteronism (PA). However, some of these subjects have low to normal aldosterone. Since low renin is driven by excessive mineralocorticoids or glucocorticoids acting on mineralocorticoid receptors (MRs), we hypothesize that a low-cortisone condition, associated classically with 11ßHSD2 deficiency, is a proxy of chronic MR activation by cortisol, which can also lead to low renin, elevated blood pressure, and renal and vascular alterations. Objective: To evaluate low cortisone as a predictor of low renin activity and its association with parameters of kidney and vascular damage. Methods: A cross-sectional study was carried out in 206 adult subjects. The subjects were classified according to low plasma renin activity (<1 ng/mL × hours) and low cortisone (<25th percentile). Results: Plasma renin activity was associated with aldosterone (r = 0.36; P < .001) and cortisone (r = 0.22; P = .001). A binary logistic regression analysis showed that serum cortisone per ug/dL increase predicted the low-renin phenotype (OR 0.4, 95% CI 0.21-0.78). The receiver operating characteristic curves for cortisone showed an area under the curve of 0.6 to discriminate subjects with low renin activity from controls. The low-cortisone subjects showed higher albuminuria and PAI-1 and lower sodium excretion. The association study also showed that urinary cortisone was correlated with blood pressure and serum potassium (P < .05). Conclusion: This is the first study showing that low cortisone is a predictor of a low-renin condition. Low cortisone also predicted surrogate markers of vascular and renal damage. Since the aldosterone to renin ratio is used in the screening of PA, low cortisone values should be considered additionally to avoid false positives in the aldosterone-renin ratio calculation.

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Primary aldosteronism (PA) and nonclassic apparent mineralocorticoid excess (NCAME) have been recognized as endocrine-related conditions having a broad clinical-biochemical spectrum, spanning from normotension to severe arterial hypertension (AHT). However, the coexistence of both phenotypes have not been reported to date. AIM: To identify and characterize clinical and biochemical parameters of subjects with both PA and NCAME conditions (NCAME&PA) and study the miRNA cargo in their urinary extracellular vesicles as potential biomarkers for this novel condition. METHODS: We performed a cross-sectional study of 206 Chilean adult subjects from a primary care cohort. We measured blood pressure (BP), cortisol (F), cortisone (E), aldosterone, plasma renin activity (PRA), microalbuminuria (MAC), plasma NGAL, MMP9, fractional-potassium-excretion (FEK). Subjects were classified as NCAME&PA, PA, NCAME, essential hypertensives (EH), or healthy controls (CTL). EV-miRNAs were quantified by Taqman-qPCR. RESULTS: We found that 30.6% subjects had an abnormal endocrine phenotype: NCAME&PA (6.8%), PA (11.2%) or NCAME (12.6%), and the prevalence of AHT was 92.9%, 82.6%, and 65%, respectively. NCAME&PA subjects had both lower cortisone (p < 0.05) and lower PRA (p < 0.0001), higher FEK (p = 0.02) and higher MAC (p = 0.01) than EH or CTL. NCAME&PA subjects had also higher NGAL levels than CTL and PA (p < 0.05). Exosome miR-192, miR-133a and miR-21 expression decreased with phenotype severity and correlated with BP and PRA (p < 0.05). CONCLUSION: We identified adult subjects with a combined condition of NCAME and PA associated with higher BP, increased renal and endothelial damage markers than control and EH. Additionally, we observed a differential expression of a specific miRNAs, suggesting a potential role of these miRNAs associated to this novel combined phenotype.

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Primary aldosteronism (PA) is an endocrine related condition leading to arterial hypertension due to inappropriately high and unregulated aldosterone concentration. Recently, a broad spectrum of PA has been recognized, which brings new challenges associated with early identification of this condition that affect renal epithelial and extrarenal tissues. Reports have shown the potential role of extracellular vesicles (EVs) and EV cargo as novel and complementary biomarkers in diagnosis and prognosis of PA. In vivo and in vitro studies have identified specific EV surface antigens, EV-proteins, and EV microRNAs that can be useful to develop novel diagnostic algorithms to detect, confirm, or follow up the PA. Moreover, the study of EVs in the field of PA provides further insight in the pathophysiological mechanism of the PA disease.

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BACKGROUND: During pregnancy, the renin-angiotensin-aldosterone system (RAAS) undergoes major changes to preserve normal blood pressure (BP) and placental blood flow and to ensure a good pregnancy outcome. Abnormal aldosterone-renin metabolism is a risk factor for arterial hypertension and cardiovascular risk, but its association with pathological conditions in pregnancy remains unknown. Moreover, potential biomarkers associated with these pathological conditions should be identified. AIM: To study a cohort of normotensive pregnant women according to their serum aldosterone and plasma renin levels and assay their small extracellular vesicles (sEVs) and a specific protein cargo (LCN2, AT1R). METHODS: A cohort of 54 normotensive pregnant women at term gestation was included. We determined the BP, serum aldosterone, and plasma renin concentrations. In a subgroup, we isolated their plasma sEVs and semiquantitated two EV proteins (AT1R and LCN2). RESULTS: We set a normal range of aldosterone and renin based on the interquartile range. We identified 5/54 (9%) pregnant women with elevated aldosterone and low renin levels and 5/54 (9%) other pregnant women with low aldosterone and elevated renin levels. No differences were found in sEV-LCN2 or sEV-AT1R. CONCLUSION: We found that 18% of normotensive pregnant women had either high aldosterone or high renin levels, suggesting a subclinical status similar to primary aldosteronism or hyperreninemia, respectively. Both could evolve to pathological conditions by affecting the maternal vascular and renal physiology and further the BP. sEVs and their specific cargo should be further studied to clarify their role as potential biomarkers of RAAS alterations in pregnant women.

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BACKGROUND: We aimed to study the associations of adipocytokines, endothelial damage markers, and high-sensitivity C-reactive protein (hs-CRP) with metabolic syndrome (MetS) components. METHODS: This cross-sectional study included 202 subjects categorized into MetS and No-MetS according to Harmonizing Adult Treatment Panel III. RESULTS: Subjects with MetS showed higher levels of proinflammatory molecules but significantly lower adiponectin levels than subjects with No-MetS. Among the studied adipocytokines, plasminogen activator inhibitor-1 (PAI-1) and adiponectin showed the strongest associations with most MetS components. PAI-1 was associated with MetS (odds ratio (OR) 1.107 (1.065-1.151), P < 0.0001), whereas adiponectin was inversely associated with MetS (OR 0.710 (0.610-0.825), P < 0.0001). Following adjustment by sex, age, body mass index, and 24-hour urinary sodium excretion in a multivariate analysis, the association of PAI-1 (OR 1.090 (1.044-1.137), P < 0.0001) and adiponectin (OR 0.634 (0.519-0.775), P < 0.0001) with MetS remained significant. Multivariate analyses supported a model in which systolic blood pressure (BP) could be predicted by PAI-1, hs-CRP, and matrix metalloproteinase 2 (R2 = 0.125; P = 0.04); diastolic BP (R2 = 0.218; P = 0.0001) and glucose (R2 = 0.074; P = 0.0001) could be predicted by PAI-1; waist circumference could be predicted by PAI-1 and hs-CRP (R2 = 0.28; P = 0.016). Receiver operating characteristic curve analysis showed that a PAI-1 concentration had the best sensitivity and specificity for discriminating subjects with MetS. CONCLUSION: PAI-1 and adiponectin rendered the most robust associations with MetS components in a general population, indicating that unfavorable adipose tissue performance is a key contributor to these metabolic anomalies. Further prospective analyses should allow establishing whether these adipocytokines can anticipate the progress of MetS and cardiovascular risk.

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Primary aldosteronism (PA) is the most common cause of secondary hypertension and reaches a prevalence of 6-10%. PA is an endocrine disorder, currently identified as a broad-spectrum phenotype, spanning from normotension to hypertension. In this regard, several studies have made advances in the identification of mediators and novel biomarkers of PA as specific proteins, miRNAs, and lately, extracellular vesicles (EVs) and their cargo. Aim: To evaluate lipocalins LCN2 and AGP1, and specific urinary EV miR-21-5p and Let-7i-5p as novel biomarkers for PA. Subjects and Methods: A cross-sectional study was performed in 41 adult subjects classified as normotensive controls (CTL), essential hypertensives (EH), and primary aldosteronism (PA) subjects, who were similar in gender, age, and BMI. Systolic (SBP) and diastolic (DBP) blood pressure, aldosterone, plasma renin activity (PRA), and aldosterone to renin ratio (ARR) were determined. Inflammatory parameters were defined as hs-C-reactive protein (hs-CRP), PAI-1, MMP9, IL6, LCN2, LCN2-MMP9, and AGP1. We isolated urinary EVs (uEVs) and measured two miRNA cargo miR-21-5p and Let-7i-5p by Taqman-qPCR. Statistical analyses as group comparisons were performed by Kruskall-Wallis, and discriminatory analyses by ROC curves were performed with SPSS v21 and Graphpad-Prism v9. Results: PA and EH subjects have significantly higher SBP and DBP (p <0.05) than the control group. PA subjects have similar hs-CRP, PAI-1, IL-6, MMP9, LCN2, and LCN2-MMP9 but have higher levels of AGP1 (p <0.05) than the CTL&EH group. The concentration and size of uEVs and miRNA Let-7i-5p did not show any difference between groups. In PA, we found significantly lower levels of miR-21-5p than controls (p <0.05). AGP1 was associated with aldosterone, PRA, and ARR. ROC curves detected AUC for AGP1 of 0.90 (IC 95 [0.79 - 1.00], p <0.001), and combination of AGP1 and EV-miR-21-5p showed an AUC of 0.94 (IC 95 [0.85 - 1.00], p<0.001) to discriminate the PA condition from EH and controls. Conclusion: Serum AGP1 protein was found to be increased, and miR-21-5p in uEVs was decreased in subjects classified as PA. Association of AGP1 with aldosterone, renin activity, and ARR, besides the high discriminatory capacity of AGP1 and uEV-miR-21-5p to identify the PA condition, place both as potential biomarkers of PA.

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BACKGROUND: Familial hyperaldosteronism type I is caused by the generation of a chimeric aldosterone synthase enzyme (ASCE) which is regulated by ACTH instead of angiotensin II. We have reported that in vitro, the wild-type (ASWT) and chimeric aldosterone synthase (ASCE) enzymes are inhibited by progesterone and estradiol does not affect their activity. AIM: To explore the direct action of testosterone on ASWT and ASCE enzymes. Material and Methods: HEK-293 cells were transiently transfected with vectors containing the full ASWT or ASCE cDNAs. The effect of testosterone on AS enzyme activities was evaluated incubating HEK-cells transfected with enzyme vectors and adding deoxycorticosterone (DOC) alone or DOC plus increasing doses of testosterone. Aldosterone production was measured by HPLC-MS/MS. Docking of testosterone within the active sites of both enzymes was performed by modelling in silico. Results: In this system, testosterone inhibited ASWT (90% inhibition at five pM, 50% inhibitory concentration (IC50) =1.690 pM) with higher efficacy andpotency than ASCE (80% inhibition at five pM, IC50=3.176 pM). Molecular modelling studies showed different orientation of testosterone in ASWT and ASCE crystal structures. CONCLUSIONS: The inhibitory effect of testosterone on ASWT or ASCE enzymes is a novel non-genomic testosterone action, suggesting that further clinical studies are needed to assess the role of testosterone in the screening and diagnosis of primary aldosteronism.

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INTRODUCTION: The multisystem inflammatory syndrome in children associated with SARS-CoV-2 (MIS-C) is cha racterized by a hyperinflammatory state resulting from a cytokine storm, evidenced by alterations in laboratory blood testing and acute-phase proteins. OBJECTIVE: to describe the clinical and labora tory characteristics of patients hospitalized due to MIS-C and identify predictive markers of severity. PATIENTS AND METHOD: Retrospective study of 32 patients. The group was divided into critical and non-critical according to clinical presentation and therapy used. Clinical and laboratory aspects were studied, including complete blood count, coagulation tests, and biomarkers. RESULTS: 18/32 were males, with a median age of 6.8 years. The most frequent manifestations were cardiovascular (84.3%), digestive (84%), and mucocutaneous (59%). The group of critical patients included 15 patients, 12 were males with a median age of 8.9 years, and the non-critical group included 17 patients, 6 were males with a median age of 5.4 years. The laboratory parameters at the admission in the global group showed increased C-reactive protein, D-dimer, leukocytes, neutrophils, ferritin, and fibrinogen. In contrast, albumin and blood sodium levels were decreased. At admission, the critical group was cha racterized by presenting thrombocytopenia, hypoalbuminemia, prolonged prothrombin time, and elevated ferritin. At the time of deterioration, there was an intensification of thrombocytopenia, in creased C-reactive protein together with increased neutrophils level. CONCLUSION: The blood count, C-reactive protein, and albuminemia at admission proved to be significantly important in the identi fication of patients at risk of clinical deterioration.

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Nonclassic apparent mineralocorticoid excess (NC-AME) is proposed as a novel clinical condition with a mild phenotypic spectrum that ranges from normotension to severe hypertension. This condition is mainly characterized by a high serum cortisol to cortisone ratio (F/E) and concomitant low cortisone (E), however further metabolic changes in NC-AME have not been studied. A cross-sectional study was performed in a primary-care cohort of 396 Chilean subjects, which were classified in two groups: NC-AME (n = 28) and healthy controls (n = 27). A discovery study based in untargeted metabolomics assay in serum samples from both groups was performed by UPLC-Q-TOF/MS. Global metabolomic variations were assayed by principal component analysis and further compared by orthogonal partial least-squares discriminant analysis (OPLS-DA). NC-AME subjects exhibited higher values of blood pressure, fractional excretion of potassium, and lower plasma renin activity and urinary sodium to potassium ratio. Metabolomic analyses showed 36 differentially regulated metabolites between NC-AME and control subjects. A ROC curve analyses identified eight metabolites with high discriminatory capacity between NC-AME and control subjects. Moreover, gamma-L-glutamyl-L-methionine sulfoxide and 5-sulfoxymethylfurfural, exhibited significant association with cortisone, which are potential biomarkers of NC-AME, however further assays should elucidate its biological role in setup and progression of this phenotype.

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CONTEXT: Primary aldosteronism (PA) represents 6% to 10% of all essential hypertension patients and is diagnosed using the aldosterone-to-renin ratio (ARR) and confirmatory studies. The complexity of PA diagnosis encourages the identification of novel PA biomarkers. Urinary extracellular vesicles (uEVs) are a potential source of biomarkers, considering that their cargo reflects the content of the parent cell. OBJECTIVE: We aimed to evaluate the proteome of uEVs from PA patients and identify potential biomarker candidates for PA. METHODS: Second morning spot urine was collected from healthy controls (n = 8) and PA patients (n = 7). The uEVs were isolated by ultracentrifugation and characterized. Proteomic analysis on uEVs was performed using LC-MS Orbitrap. RESULTS: Isolated uEVs carried extracellular vesicle markers, showed a round shape and sizes between 50 and 150 nm. The concentration of uEVs showed a direct correlation with urinary creatinine (r = 0.6357; P = 0.0128). The uEV size mean (167 ±â€…6 vs 183 ±â€…4nm) and mode (137 ±â€…7 vs 171 ±â€…11nm) was significantly smaller in PA patients than in control subjects, but similar in concentration. Proteomic analysis of uEVs from PA patients identified an upregulation of alpha-1-acid glycoprotein 1 (AGP1) in PA uEVs, which was confirmed using immunoblot. A receiver operating characteristic curve analysis showed an area under the curve of 0.92 (0.82 to 1; P = 0.0055). CONCLUSION: Proteomic and further immunoblot analyses of uEVs highlights AGP1 as potential biomarker for PA.

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BACKGROUND: Familial hyperaldosteronism type I is caused by the generation of a chimeric aldosterone synthase enzyme (ASCE) which is regulated by ACTH instead of angiotensin II. We have reported that in vitro, the wild-type (ASWT) and chimeric aldosterone synthase (ASCE) enzymes are inhibited by progesterone and estradiol does not affect their activity. AIM: To explore the direct action of testosterone on ASWT and ASCE enzymes. MATERIAL AND METHODS: HEK-293 cells were transiently transfected with vectors containing the full ASWT or ASCE cDNAs. The effect of testosterone on AS enzyme activities was evaluated incubating HEK-cells transfected with enzyme vectors and adding deoxycorticosterone (DOC) alone or DOC plus increasing doses of testosterone. Aldosterone production was measured by HPLC-MS/MS. Docking of testosterone within the active sites of both enzymes was performed by modelling in silico. RESULTS: In this system, testosterone inhibited ASWT (90% inhibition at five pM, 50% inhibitory concentration (IC50) =1.690 pM) with higher efficacy andpotency than ASCE (80% inhibition at five pM, IC50=3.176 pM). Molecular modelling studies showed different orientation of testosterone in ASWT and ASCE crystal structures. CONCLUSIONS: The inhibitory effect of testosterone on ASWT or ASCE enzymes is a novel non-genomic testosterone action, suggesting that further clinical studies are needed to assess the role of testosterone in the screening and diagnosis of primary aldosteronism.

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Resumen Introducción: La infección por virus SARS-CoV-2 responsable de la pandemia actual, es una entidad clínica y fisiopatológica nueva y en desarrollo, cuyo control aún es incierto mientras no contemos con una vacuna efectiva y de distribución universal. Descrita inicialmente como una enfermedad respiratoria mayoritariamente de adultos, los niños también pueden enfermar y se ha visto que en ellos las manifestaciones clínicas de enfermedad suelen diferir a las de los adultos expresándose como cuadros benignos en su mayoría. Si requieren hospitalización o algún tipo de asistencia, el cuadro se resuelve con tratamiento de soporte y sin complicaciones, mayoritariamente. Sin embargo, en el síndrome inflamatorio multisistémico asociado a COVID-19 (SIM-C) es de vital importancia la sospecha precoz y la derivación a un centro de alta complejidad para otorgar el soporte y tratamiento adecuado para lograr una buena y adecuada sobrevida. Objetivo: Describir el espectro clínico de enfermedad por virus SARS-CoV-2 en un centro de referencia pediátrico con la pandemia aún en desarrollo. Método: Se presenta la casuística de 537 pacientes con infección por SARS-CoV-2 atendidos entre marzo 1 y julio 15, 2020, con descripción de aquellos que fueran hospitalizados. Resultados: 127 (23%) de ellos fueron internados y de éstos 69% sintomáticos. Veintiséis pacientes (20%) de los hospitalizados presentaron SIM-C y sólo uno falleció por complicaciones de sus patologías de base.

Abstract Background: SARS-CoV-2 virus infection responsible for de pandemic in course, is a new clinical and physiopathological entity, whose control is still uncertain till we can provide an effective and universal vaccine. In the beginning it was described as a respiratory disease which affects mainly adults, children can have the disease too and in this group the disease can be different than the adult disease. Acute infection in children is mostly mild and when it requires hospital assistance it resolves with support therapy and without complications most of the time. However, in the Pediatric Inflammatory Multisystemic Syndrome is vital the early clinical suspect and refers to a tertiary center to bring support and properly treatment. Aim: To describe the clinical spectrum of SARS-CoV-2 virus disease in a pediatric referral center with the pandemic still in development. Method: A case series of 537 patients with SARS-CoV-2 infection treated between March 1 and July 15, 2020 is presented with a description of those who were hospitalized. Results: 127 (23%) of them were hospitalized and of these 69% were symptomatic. Twenty-six patients (20%) of those hospitalized presented PIMS, only one died for complications of his chronic diseases.

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CONTEXT: Arterial hypertension (AHT) is one of the most frequent pathologies in the general population. Subtypes of essential hypertension characterized by low renin levels allowed the identification of 2 different clinical entities: aldosterone-mediated mineralocorticoid receptor (MR) activation and cortisol-mediated MR activation. EVIDENCE ACQUISITION: This review is based upon a search of Pubmed and Google Scholar databases, up to August 2019, for all publications relating to endocrine hypertension, apparent mineralocorticoid excess (AME) and cortisol (F) to cortisone (E) metabolism. EVIDENCE SYNTHESIS: The spectrum of cortisol-mediated MR activation includes the classic AME syndrome to milder (nonclassic) forms of AME, the latter with a much higher prevalence (7.1%) than classic AME but different phenotype and genotype. Nonclassic AME (NC-AME) is mainly related to partial 11ßHSD2 deficiency associated with genetic variations and epigenetic modifications (first hit) and potential additive actions of endogenous or exogenous inhibitors (ie, glycyrrhetinic acid-like factors [GALFS]) and other factors (ie, age, high sodium intake) (second hit). Subjects with NC-AME are characterized by a high F/E ratio, low E levels, normal to elevated blood pressure, low plasma renin and increased urinary potassium excretion. NC-AME condition should benefit from low-sodium and potassium diet recommendations and monotherapy with MR antagonists. CONCLUSION: NC-AME has a higher prevalence and a milder phenotypical spectrum than AME. NC-AME etiology is associated to a first hit (gene and epigene level) and an additive second hit. NC-AME subjects are candidates to be treated with MR antagonists aimed to improve blood pressure, end-organ damage, and modulate the renin levels.

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BACKGROUND: SARS-CoV-2 virus infection responsible for de pandemic in course, is a new clinical and physiopathological entity, whose control is still uncertain till we can provide an effective and universal vaccine. In the beginning it was described as a respiratory disease which affects mainly adults, children can have the disease too and in this group the disease can be different than the adult disease. Acute infection in children is mostly mild and when it requires hospital assistance it resolves with support therapy and without complications most of the time. However, in the Pediatric Inflammatory Multisystemic Syndrome is vital the early clinical suspect and refers to a tertiary center to bring support and properly treatment. AIM: To describe the clinical spectrum of SARS-CoV-2 virus disease in a pediatric referral center with the pandemic still in development. METHOD: A case series of 537 patients with SARS-CoV-2 infection treated between March 1 and July 15, 2020 is presented with a description of those who were hospitalized. RESULTS: 127 (23%) of them were hospitalized and of these 69% were symptomatic. Twenty-six patients (20%) of those hospitalized presented PIMS, only one died for complications of his chronic diseases.

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PURPOSE: 21-hydroxylase deficiency (21-OHD) is a congenital adrenal disease with more than 200 mutations published to date. The aim of this report is to describe a severe novel mutation of the CYP21A2 gene. METHOD: We describe a case of a 39-year-old male diagnosed with a salt wasting congenital adrenal hyperplasia (SWCAH) due to 21-OHD. The genetic testing was done using a combination of three methods (PCR XL, SALSA-MLPA, and bidirectional sequencing) and finally an in silico analysis. RESULTS: The genetic testing demonstrated three severe mutations of the CYP21A2 gene (p.Gln318*; c.290-13C>G; and p.Trp86*), being the last one a novel mutation not previously reported. The in silico modeling of the p.Trp86* (c.258G>A) showed a truncated CYP21A2 protein that loses all the main structural features required for activity, such as the HEM binding domain and the hormone binding site. CONCLUSION: We present an adult man with an SWCAH due to 21-OHD who carried three severe mutations of the CYP21A2 gene, one of them, p.Trp86* (c.258G>A) has not been previously described.

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BACKGROUND: The "nonclassic" apparent mineralocorticoid excess (NC-AME) has been identified in approximately 7% of general population. This phenotype is characterized by low plasma renin activity (PRA), high serum cortisol (F) to cortisone (E) ratio, low cortisone, high Fractional Excretion of potassium (FEK) and normal-elevated systolic blood pressure (SBP). An early detection and/or identification of novel biomarkers of this phenotype could avoid the progression or future complications leading to arterial hypertension. Isolation of extracellular vesicles, such as exosomes, in specific biofluids support the identification of tissue-specific RNA and miRNA, which may be useful as novel biomarkers. Our aim was to identify miRNAs within urinary exosomes associated to the NC-AME phenotype. METHODS: We perform a cross-sectional study in a primary care cohort of 127 Chilean subjects. We measured BP, serum cortisol, cortisone, aldosterone, PRA. According to the previous reported, a subgroup of subjects was classified as NC-AME (n = 10). Urinary exosomes were isolated and miRNA cargo was sequenced by Illumina-NextSeq-500. RESULTS: We found that NC-AME subjects had lower cortisone (p < 0.0001), higher F/E ratio (p < 0.0001), lower serum potassium (p = 0.009) and higher FEK 24 h (p = 0.03) than controls. We found miR-204-5p (fold-change = 0.115; p 0.001) and miR-192-5p (fold-change = 0.246; p 0.03) are both significantly downregulated in NC-AME. miR-192-5p expression was correlated with PRA (r = 0.45; p 0.028) and miR-204-5p expression with SBP (r = - 0.48, p 0.027) and F/E ratio (r = - 0.48; p 0.026). CONCLUSIONS: These findings could support a potential role of these miRNAs as regulators and novel biomarkers of the NC-AME phenotype.

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